RESUMO
The close link between metabolism and cell death has been getting more and more attention.Many metabolically related proteins play a key role in the programmed cell death pathway.Several proteins classically regulating cell death have been found to regulate metabolism.In addition,many metabolic intermediates are closely involved in the cascade of signal transduction pathways that influence cell death.Some metabolic checkpoints not only receive information from metabolic variables,but also transmit signals that regulate cell survival.Typically,these checkpoints respond to metabolic imbalances by activating an organelle specific or by initiating an adaptive response at the overall level of the cell,and attempts to establish a new homeostasis.However,when the metabolic disorders are extravagantly serious or prolonged in time,these checkpoints will initiate apoptosis or programmed cell death.The cross-regulation of cellular metabolism and death pathways was discussed,so as to provide clues for the development of novel pharmacological approaches by regulating the metabolism to block or induced cell death.
RESUMO
Telomeres are protective caps located at the ends of human chromosomes. Telomeres shorten with each successive cell di-vision in normal human cells, whereas they are continuously elongated by human telomerase in over 85%of tumors. This simple and attractive difference steers the development of anticancer drugs targeting telomeres and telomerase. Many promising current telo-mere/telomerase-targeting agents, such as GRN163L and GV1001, showed good therapeutic effect both in preclinical studies and phaseⅠ/Ⅱclinical trials. These agents have even entered phaseⅢclinical trials in patients with various tumors. Most therapeutics are more effective when used in combination with standard chemotherapies. Moreover, pharmacological interference with tumor-cell telomere biology to reduce telomere length and/or telomere stability could enhance the effectiveness and safety of radiotherapy. Therapeutics targeting telomere/telomerase may play a key role in radiotherapy in the era of personalized medicine in the future.
RESUMO
BACKGROUND: Activator protein 2 gamma (AP-2gamma) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2gamma has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis. METHODS: To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2gamma binding sites on genomic DNA from human breast cancer cell line MDA-MB-453. RESULTS: 20 novel DNA fragments proximal to potential AP-2gamma targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2gamma target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2gamma. Decreased expression and overexpression of AP-2gamma in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2gamma directly regulates them. CONCLUSION: This suggested that AP-2gamma can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future.
